The Pro-Tumor Biological Function of IL-36α Plays an Important Role in the Tumor Microenvironment of HCC.
To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -β, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer. In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro. Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1β, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis. Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.


Note: Single-shot continuously time-resolved MeV ultrafast electron diffraction.
We have demonstrated single-shot continuously time-resolved MeV ultrafast electron diffraction using a static single crystal gold sample. An MeV high density electron pulse was used to probe the sample and then streaked by an rf deflecting cavity. The single-shot, high quality, streaked diffraction pattern allowed structural information within several picoseconds to be continuously temporally resolved with an approximately 200 fs resolution. The temporal resolution can be straightforwardly improved to 100 fs by increasing the streaking strength. We foresee that this system would become a powerful tool for ultrafast structural dynamics studies.


Local and systemic immune response in rabbits after intraintestinal immunization with a double-marker attenuated strain of Salmonella typhimurium.
Local and systemic immune response was studied in 3 groups of rabbits immunized and reimmunized 190 days later with S. typhimurium double-marker attenuated strain 1,771 and doses ranged from 20.10(9) to 0.2.10(9) cells. Another group of rabbits was immunized with extract (hydroxylammine) vaccine. It was found that the attenuated strain persisted for considerable time in the gut, and induced pronounced and continuous immune response as measured by the passive hemagglutination test. The serum antibody response had the character of a secondary one with switching on the synthesis of IgM to IgG already after basic immunisation. By the Coombs' technique it was shown that specific immunoglobulins demonstrated in feces were secretory antibodies of the class IgA (SIgA). The immune response developed after reimmunization was still more vigorous and prolonged pointing to an immune memory existance. It was possible to obtain well manifested immunity with the lowest dose. The extract vaccine revealed only weak and transitory serum and intestinal antibody levels without SIgA appearance. The results obtained in this setup make S. typhimurium 1771 a perspective candidate for a live vaccine.


Progressive Paraplegia from Spinal Cord Stimulator Lead Fibrotic Encapsulation: A Case Report.
Ten years after placement of a spinal cord stimulator (SCS) and resolution of pain, this patient presented with progressive paraplegia, worsening thoracic radicular pain at the same dermatome level of the electrodes, and bowel and bladder incontinence. Computed tomographic myelogram confirmed thoracic spinal cord central canal stenosis at the level of electrodes. After removal of the fibrotic tissue and electrodes, the patient had resolution of his thoracic radicular pain and a return of his pre-SCS pain and minimal neurologic and functional return. To the authors' knowledge, no studies have been identified with thoracic SCS lead fibrosis in the United States causing permanent paraplegia. Only one other case has been reported in Madrid, Spain. Patients with SCS presenting with loss of pain relief, new-onset radicular or neuropathic pain in same dermatome(s) as SCS electrodes, worsening neuromuscular examination, or new bladder or bowel incontinence need to be evaluated for complications regarding SCS implantation causing spinal stenosis and subsequent cord compression to avoid permanent neurologic deficits.


Higher mineralized bone volume is associated with a lower plain X-Ray vascular calcification score in hemodialysis patients.
In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score. In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were assessed by the simple vascular calcification score (SVCS) in plain X-Ray of pelvis and hands and, for comparison, by the Agatston score in Multi-Slice Computed Tomography (MSCT). SVCS≥3 was present in 20 patients (40%). Low and high bone turnover were present in 54% and 38% of patients, respectively. Low bone volume was present in 20% of patients. In multivariable analysis, higher age (p = 0.015) and longer hemodialysis duration (p = 0.017) were associated with SVCS≥3. Contrary to cancellous bone volume, the addition to this model of mineralized bone volume (OR = 0.863; 95%CI: 0.766, 0.971; p = 0.015), improved the performance of the model. For each increase of 1% in mineralized bone volume there was a 13.7% decrease in the odds of having SVCS≥3 (p = 0.015). An Agatston score>400 was observed in 80% of the patients with a SVCS≥3 versus 4% of patients with a SVCS<3, (p<0.001). Higher mineralized bone volume was associated with a lower plain X-ray vascular calcification. This study corroborates the hypothesis of the existence of a link between bone and vessel and reinforces the clinical utility of this simple and inexpensive vascular calcification score in dialysis patients.


Variations in food security status and associated factors: a comparative study across rural-urban interface in north of Bengaluru.
The paper makes an attempt to analyze the food consumption pattern, food security status, and factors influencing food security. The study revealed that, among different items of consumption, the use of cereals was higher among the households across the gradients. Rural households derived most of their calorie from cereals. Across rural-urban interface, total consumption was relatively higher in urban area (38.44 kg/CU/month) followed by transition and rural areas. The total energy derived from the consumption of different food items was the highest in urban area (2491.90 Kcal/capita/day) followed by transition (2415.82 Kcal/capita/day) and rural area (2383.28 Kcal/capita/day). The households residing in urban area showed higher Simpson Index of Dietary Diversity (0.81) followed by transition (0.80) and rural (0.77) areas. The percentage of food secure households was highest in urban areas (76.25%) followed by transition (63.75%) and rural (58.75%) areas. Regression analysis revealed that education, monthly income of the sample households, and their localization in urban area were significant determinants of food security. The study concludes the prevalence of food insecurity and suggested the need for strengthening existing food security programmes, besides creating awareness among households to move toward balanced diet by diversifying their production, income, and consumption pattern.


Exposure to sub-inhibitory concentrations of cefotaxime enhances the systemic colonization of Salmonella Typhimurium in BALB/c mice.
It has been proposed that sub-inhibitory concentrations of antibiotics play a role in virulence modulation. In this study, we evaluated the ability of Salmonella enterica serovar Typhimurium (hereafter S. Typhimurium) to colonize systemically BALB/c mice after exposure to a sub-inhibitory concentration of cefotaxime (CTX). In vivo competition assays showed a fivefold increase in systemic colonization of CTX-exposed bacteria when compared to untreated bacteria. To identify the molecular mechanisms involved in this phenomenon, we carried out a high-throughput genetic screen. A transposon library of S. Typhimurium mutants was subjected to negative selection in the presence of a sub-inhibitory concentration of CTX and genes related to anaerobic metabolism, biosynthesis of purines, pyrimidines, amino acids and other metabolites were identified as needed to survive in this condition. In addition, an impaired ability for oxygen consumption was observed when bacteria were cultured in the presence of a sub-inhibitory concentration of CTX. Altogether, our data indicate that exposure to sub-lethal concentrations of CTX increases the systemic colonization of S. Typhimurium in BALB/c mice in part by the establishment of a fitness alteration conducive to anaerobic metabolism.


Voluntary and Spontaneous Smile Quantification in Facial Palsy Patients: Validation of a Novel Mobile Application.
Introduction: Restoration of spontaneous smiling is a key goal in facial reanimation. A major obstacle to quantifying recovery of spontaneous smiling is the current lack of a uniform and objective means of smile quantification. Objective: To compare the facial movements during smiling in patients with facial paralysis as measured by an automated application and human observers. Methods: Video recordings of 25 patients with unilateral facial palsy (FP) watching humorous videos were utilized. Application-derived smile timestamping was compared with manual observer interpretation. Internal reliability of measurements was evaluated through a test-retest approach. Results: Application-derived smile identification demonstrated almost perfect agreement with manual interpretation (kappa 0.861, p < 0.001). There was no statistically significant difference in mean number of smiles between detection method (p = 0.354). Automated smile identification demonstrated a high degree of specificity (95.4%), accuracy (93.1%), positive-predictive value (94.7%), and negative-predictive value (91.8%). This method demonstrated a high degree of reliability (kappa 0.864, p < 0.01). Conclusion: The novel "SmileCheck" mobile phone application performed accurate and reliable smile quantification in FP patients in comparison with manual observation.


Nursing interventions with people with obesity in Primary Health Care: an integrative review.
Objective Identify the knowledge produced on nursing interventions with people suffering from obesity in Primary Health Care. Method Integrative literature review of publications indexed in the databases: CINAHL, LILACS, MEDLINE, SciELO, SCOPUS and WEB OF SCIENCE, between 2011 and 2016. Results Thirty-three articles were selected. The knowledge produced covered two themes: "Counseling aimed at weight control and promotion of healthy lifestyle habits" and "Perception of Primary Health Care nurses regarding interventions with people with obesity." Conclusion The results may help prompt reflections on professional training, management, and health services in terms of the relevance of nurses working with people suffering from obesity, with the support of digital technologies, motivational techniques, and nursing consultations. This could enhance their activities in the multiprofessional teams in which they participate at this healthcare level.


Chronic cutaneous candidiasis in bottle-nosed dolphins.
In a 20-month period, generalized chronic cutaneous candidiasis developed in 3 performing bottle-nosed dolphins kept in an indoor pool. Extensive esophagogastric ulcerations were observed in 2 of the dolphins, each of which died, presumably because of these lesions. The 3rd dolphin died during a surgical procedure and did not have any esophagogastric ulcerations. Candida albicans was the only organism isolated from skin lesions but was not isolated from adjacent normal skin of dolphins. Treatment with antifungal drugs was unsuccessful. Subsequently, immunopotentiating treatment with levamisole phosphate resulted in formation of granulation tissue and healing of the skin lesions.


Pharmacokinetics of the major metabolites of D-penicillamine in patients with rheumatoid arthritis.
The pharmacokinetic disposition of D-penicillamine and its major metabolites, penicillamine cysteine disulfide ( PSSC ) and penicillamine disulfide ( PSSP ) has been studied in eight patients with rheumatoid arthritis. Plasma concentrations of D-penicillamine, PSSP and PSSC displayed similar characteristics in terms of times to maximum concentrations and biphasic elimination from plasma. Initial t1/2 (alpha) phase ranged from 0.86 to 4.41 h for parent drug and 0.81 to 4.41 h for metabolites. Final t1/2 (beta phase) ranged from 3.4 to 9.45 h for D-penicillamine and 5.62 to 21.7 h for the metabolites. Total drug and metabolites detected in urine accounted for 12.0 to 48.7% of oral drug.


Development of Tetrameric N-Annulated Perylene Diimides Using "Click" Chemistry.
Herein, we report the design, synthesis, and characterization of two novel N-annulated perylene diimide (NPDI) tetramer arrays that were developed using copper catalyzed alkyne-azide cycloaddition. Despite the optoelectronic properties of both tetramers being nearly identical, the two tetramers exhibited very different molecular geometries. The twisted spirobifluorene NPDI tetramer (sbfNPDI4 ) was found to have an extended and flexible geometry, while the planar pyrene NPDI tetramer (pyrNPDI4 ) exhibited a highly congested and conformationally locked geometry. Organic photovoltaic devices were constructed to demonstrate the use of both new compounds as electron acceptor materials, where slightly higher power conversion efficiencies were achieved with pyrNPDI4 than sbfNPDI4 . This study highlights the viability of using "click" chemistry as a facile synthetic strategy towards the development of new multicomponent perylene diimide materials for organic electronic applications.


Behavioral adjustment of psychiatric hospital patients and helping behavior.
This study investigated the relationship between behavioral adjustment of mental hospital patients and helping behavior in two distinctly different controlled situations. Forty hospitalized male patients between the ages of 20 and 45 were assigned to two groups of equal size according to ratings they received on the MACC Behavioral Adjustment Scale. Each subject was exposed to two separate and independent experimental situations calling for helping behavior. Helping in the first situation was defined as offering a confederate the use of an extra pencil, while in the second it was defined as offering to help a confederate in the hallway to pick up a box of pencils that had just been dropped. The results of both experiments confirmed the hypothesis that persons suffering more severe levels of disturbance and maladjustment perform significantly fewer helpful acts. Results were discussed in terms of empathy, self-concern, and response cost. Also some implications for treatment were discussed.


Variants of the rat basophilic leukemia cell line for the study of histamine release.
Cloning of the rat basophilic leukemia (RBL) cell lines demonstrates variability in cell chromosome number (approximately 44-70) and in their capacity to release histamine following an IgE- or Ca2+-ionophore stimulus. After IgE activation there is increased phospholipid methylation, Ca2+ influx, arachidonic acid, and histamine release. On Ca2+ ionophore A23187 stimulation, phospholipid methylation is not increased, but Ca2+ influx, arachidonic acid, and histamine release occur. Variants of the RBL-cloned sublines defective at different stages in the release process were obtained and used to sequence the different events in the release process: IgE activation is followed by methylation, Ca2+ influx, arachidonic acid, and histamine release. However, there are other variants with defects in intermediate steps in the pathway, e.g., increased phospholipid methylation that is not followed by Ca2+ influx or arachidonic acid release not followed by histamine release. Isolating variants carrying drug-resistance markers made hybridization (reconstitution) experiments possible. Two variants were recognized, each of which was deficient in one of the two phospholipid methyltransferase enzymes. Neither of these two variants released histamine; hybrids formed by fusion of these two cell lines have both phospholipid methyltransferase enzymes and release histamine. By other complementation experiments, groups of variants with defects at different steps in the histamine release sequence were recognized. Clearly, these basophilic leukemia cell lines provide a unique system for the study of the mechanism of histamine release.


Fluorine-18-Labeled Diaryl-azines as Improved β-Amyloid Imaging Tracers: From Bench to First-in-Human Studies.
The deposition of β-amyloid (Aβ) in the brain is a pathologic hallmark of Alzheimer's disease (AD), appearing years before the onset of symptoms, and its detection is incorporated into clinical diagnosis. Here, we have discovered and developed a class of diaryl-azine derivatives for detecting Aβ plaques in the AD brain using PET imaging. After a set of comprehensive preclinical assessments, we screened out a promising Aβ-PET tracer, [18F]92, with a high binding affinity to the Aβ aggregates, significant binding ability with the AD brain sections, and optimal brain pharmacokinetic properties in rodents and non-human primates. The first-in-human PET study declared that [18F]92 displayed low white matter uptake and could bind to Aβ pathology for distinguishing AD from healthy control subjects. All these results support that [18F]92 might become a promising PET tracer for visualizing Aβ pathology in AD patients.


Effect of thymoquinone on head and neck squamous cell carcinoma cells in vitro: Synergism with radiation.
Thymoquinone (TQ) is the main bioactive constituent present in black seed oil (Nigella sativa); it has shown anti-inflammatory and anti-neoplastic effects in various cancer cell types. The aim of the present study was to investigate the effects of TQ on head and neck squamous cell carcinoma (HNSCC) cell lines, on its own and in combination with radiation and cisplatin, respectively. The SCC25 and CAL27 HNSCC cell lines were treated with TQ alone and in combination with cisplatin or radiation, respectively. Proliferation assays and clonogenic assays were performed. Apoptosis was detected by flow cytometry. TQ exhibited dose-dependent cytotoxicity via apoptosis in the investigated cell lines. In combination with cisplatin, TQ resulted in no significant increase in cytotoxicity. Combined with radiation, TQ significantly reduced clonogenic survival compared with each treatment method alone. TQ is a promising agent in the treatment of head and neck cancer due to its anti-proliferative and radiosensitizing properties. However, the combination of TQ with cisplatin showed no therapeutic benefit in vitro.


Knowledge, Attitude, and Practice of Diabetic Foot Ulcer Care in Asser Region: A Cross-Sectional Study.
Background Foot problems continue to be the leading cause of hospital admissions among people with diabetes. The objective of this study was to explore and assess the knowledge and attitudes of individuals about diabetic foot ulcers in the Asser region, Saudi Arabia. Methodology An anonymous, online, cross-sectional survey was conducted. The questionnaire was distributed through commonly used social media platforms such as Instagram, Facebook, and Twitter. Results A total of 445 participants were included in this survey. Overall, 37.1% (165) were aged 18-25 years, 64.3% (286) were women, and 75.7% (337) had university-level education. A significant number of participants had relatives with diabetes (57.1%, 254), while a smaller percentage reported having diabetes themselves (7.3%, 33), and a substantial proportion were neither diabetic nor had a relative with diabetes (35.6%, (158). Nearly two-fifths of the participants (37.8%, 168) received information about diabetes and diabetic foot care from physicians, and 34.1% (152) of the participants accessed information online. There were significant differences between those who did not have diabetes mellitus (DM) and those who had DM or whose relatives were diabetic in responses to the following questions: "Do you think that diabetes may cause gangrene in the foot?" (50.9% (205) vs. 45.7% (32), p = 0.019), "Do you think that preventing diabetic foot ulcers is more important than treating diabetic foot ulcers?" (60.8% (228) vs. 46.9% (60), p = 0.002), and "Do you think it is important to constantly monitor diabetic foot wounds?" (63.1% (200) vs. 30.4% (17), p < 0.001). There was a statistically significant difference between groups in the practice of daily foot checks, washing feet, moisturizing feet, keeping feet away from hot and cold, and nail care (p < 0.001). Conclusions The participants in the study showed a lack of knowledge regarding diabetic foot care, indicating the potential for better outcomes through the implementation of enhanced health education programs.


Bridging the chronic care gap: HealthOne Mt Druitt, Australia.
HealthOne was part of a state-wide initiative to invest in new community-based facilities for collocating services. The HealthOne Mount Druitt is a virtual hub and spoke organisation established in 2006 in a socially disadvantaged part of Western Sydney based out of a new community health hub. The model is based on 'virtual' care planning and aims to improve coordination of care for older people with complex health needs, reduce unnecessary hospitalisations and ensure appropriate referral to community and specialist health services. General practitioner liaison nurses (GPLNs) work closely with clients as well as general practitioners (GPs) and other health care providers. Primary health care providers reported improved communication and coordination of services, and there have been lower levels of utilisation of the emergency department (ED) for patients following enrolment in the programme. HealthOne provides an example of how a virtual organisation together with highly skilled care coordinators can overcome some of the barriers to providing integrated care created by fragmented funding streams and care delivery systems.


Origin, dispersal and genomic structure of a low-copy-number hypervariable RFLP clone in Triticum and Aegilops species.
The genome of common wheat has evolved through allopolyploidization of three ancestral diploid genomes. A previously identified restriction fragment length polymorphism (RFLP) marker, pTag546, has the unique feature of showing hypervariability among closely related common wheat cultivars. To understand the origin and the mode of dispersal of this hypervariable sequence in the wheat genome, the distribution and structure of the homologous sequences were studied using ancestral diploid species, tetraploid disomic substitution lines and synthetic hexaploid lines. Comparative Southern blot and PCR analyses suggested that pTag546 homologs in the tetraploid and hexaploid wheat were derived from the S genome of Aegilops speltoides. Some pTag546 homologs were found to have transposed to A and D genomes in polyploid wheat. Evidence of transposition and elimination in some synthetic hexaploid lines was also obtained by comparing their copy numbers with those in the parental lines. Southern blot analysis of a genomic clone using a contiguous subset of sequences as probes revealed a core region of hypervariability that coincided with the region containing pTag546. No obvious structural characteristics that could explain the hypervariability, however, were found around the pTag546 sequence, except for accumulation of small repetitive sequences at one border. It was concluded that pTag546 increased its copy number through yet unknown mechanism(s) of transposition to various chromosomal locations over the period of allopolyploid evolution and during the artificial genome manipulation in wheat.


Carboplatin-induced hypersensitivity reaction.
We describe a 65-year-old female with relapsed ovarian cancer who developed a severe hypersensitivity reaction during the second cycle of carboplatin treatment. The patient developed respiratory failure, acute respiratory distress syndrome and hypotension, requiring admission to the intensive care unit.


Conduction velocity and refractory period of single motor nerve fibres in motor neuron disease.
Electromyographic single motor unit recordings were used to study the axonal conduction velocity and the axonal refractory period of 60 motor units in patients with severe motor neuron disease. Eighteen per cent of the motor units had abnormally low axonal conduction velocity probably due to secondary degenerative changes. Thirty-two per cent of the motor units had abnormally long axonal refractory period but normal conduction velocity. Whether this reflects a primary disease mechanism or secondary changes remains to be established.


Clinical Outcomes of Mixed Response to Pembrolizumab in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.
Despite the presence of a mixed response (MR) in patients with urothelial carcinoma (UC) who receive immune checkpoint inhibitors, the clinical outcome of these patient has not been reported. We evaluated the clinical outcome of MR to pembrolizumab for advanced UC. Advanced UC patients who received pembrolizumab after platinum-based chemotherapy failure with measurable disease in multiple organs were retrospectively analyzed. Among 31 patients, MR [including progressive disease (PD)+complete response (CR) or partial response (PR)] was confirmed in 4 (12.9%). The median overall survival (OS) of the CR+PR (including CR+SD±PR), stable disease (SD), PD (including PD±SD) and MR groups was 16.0, 5.1, 5.4 and 4.3 months, respectively. There was no significant difference in the OS between the MR and CR+PR response groups (log-rank test, p=0.069). A mixed response to pembrolizumab in advanced UC was not uncommon. Despite the non-significant difference in the OS between the mixed and CR+PR response groups, the OS of the MR group tended to be similar to that of the SD and PD response groups.


Agreement of body adiposity index (BAI) and paediatric body adiposity index (BAIp) in determining body fat in Brazilian children and adolescents.
To evaluate agreement of the body adiposity index (BAI) and paediatric body adiposity index (BAIp) in estimating body fat compared with dual-energy X-ray absorptiometry (DXA) and to propose cut-off points for these indices to classify excess adiposity in Brazilian children and adolescents. Cross-sectional study. Measures of weight, height, hip circumference, BMI and body fat percentage (%BF) assessed by DXA were taken, and BAI and BAIp were calculated. The Bland-Altman plot was used to estimate agreement between the methods, and the receiver-operating characteristic curve to determine the cut-off points for BAI and BAIp per age and sex in comparison with DXA. Viçosa, Minas Gerais, Brazil. Children and adolescents aged 8-19 years (n 1049). Of the children and adolescents, 52·4 % were girls. BAI and BAIp had satisfactory performance by the receiver-operating characteristic curve, except for the 18-19 years age group, whose BAIp had better predictive capacity than BAI. The agreement analysis showed that BAI overestimated %BF by 2·64 %, on average, using DXA; while BAIp underestimated %BF by 3·37 %. BAI and BAIp showed low agreement with the body fat obtained by DXA, requiring caution when interpreting body composition data in children and adolescents.


Impact of the Primary Information Source Used for Decision Making on Treatment Perceptions and Regret in Prostate Cancer.
To assess the impact of the primary source of information used by prostate cancer patients to select a radiation treatment on their overall treatment experience and on treatment regret. Patients with low to favorable intermediate-risk prostate cancer treated with stereotactic body radiation therapy, intensity-modulated radiation therapy, or high-dose rate brachytherapy were surveyed. The questionnaire explored the decision-making experience, treatment experience, and treatment regret. In total, 322 consecutive patients were surveyed with an 86% (n=276) response rate. In total, 48% (n=132) selected their radiation oncologist as the primary information source, 23% (n=62) selected their urologist, 16% (n=44) selected the Internet, 6% (n=17) selected other patients, and 8% (n=21) selected other. In total, 39% of patients who selected the Internet as their primary information source reported their actual treatment experience to be worse than expected versus 13% of respondents who selected their urologist, 12% who selected other patients, and 2% who selected their radiation oncologist (P<0.01). Similarly, 43% who selected the Internet as their primary information source endorsed treatment regret versus 10% who selected their urologist, and 7% who selected their radiation oncologist (P<0.01). On multivariate regression, only patients who selected the Internet as their primary information source were more likely to endorse treatment regret (odds ratio, 46.47; P<0.001) and a worse treatment perception (odds ratio, 83.33; P<0.001). Patients who used the Internet as their primary information source were significantly more likely to endorse treatment regret and a worse than expected overall treatment experience. These data highlight the potential dangers of Internet-based resources and the importance for physicians to proactively counsel patients.


Expression levels of interferon-ɣ and type 2 deiodinase in patients diagnosed with recurrent depressive disorders.
Thyroid hormones (TH) are involved in modulation of the immune system and inflammation. TH dysregulation is associated with depressive disorders. The iodothyronine deiodinases (DIOs), the key enzymes for TH synthesis, can be affected and induced by pro-inflammatory cytokines. We aimed to investigate the levels of and correlation between type 2 DIO (DIO2) and interferon-gamma (IFN-ɣ) in patients with recurrent depressive disorders (rDD). Data from 91 rDD patients and 105 healthy controls were analyzed. The diagnoses are based on the ICD-10 criteria (F33.0-F33.8). Expression levels of DIO2 and IFN-ɣ were estimated using the method based on the polymerase chain reaction and the enzyme-linked immunosorbent assay (ELISA). The DIO2 expression on mRNA/protein levels in rDD patients (both female and males) was reduced as compared with the control subjects. No correlation between DIO2 and IFN-ɣ expression was observed. This is the first study to reveal that one may cautiously suggest that DIO2 may be involved in the development and/or progression of rDD. The mechanisms of TH regulation on depression, however, need further investigation.


Mycobacterium mageritense tattoo infection: a known complication with a novel species.
Non-pigmented rapidly growing mycobacteria are nontuberculous mycobacteria (NTM) capable of producing disease. We report a case of tattoo-associated NTM infection with a novel species: Mycobacterium mageritense. A 48-year-old man presented with a two-week history of a papulopustular eruption on the shaded areas of a tattoo that had been placed five weeks prior while in the Philippines. Histopathology from punch biopsies revealed suppurative granulomatous dermatitis with acid fast bacilli present. Subsequent matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometer identified the bacteria as Mycobacterium margeritense. After consultation with infectious disease specialists and culture susceptibilities, the patient was treated with three months of dual antibiotic therapy with minocycline and moxifloxacin. The patient experienced a slow but complete resolution of clinical skin findings after the course of treatment. Since discovery in 1997, M. mageritense infection has been demonstrated in a wide spectrum of disease, predominantly skin and soft tissue infections. The species has not been previously implicated in tattoo-associated NTM infections. M. mageritense should be considered as a specific type of mycobacteria in the differential diagnosis for tattoo-associated NTM infections owing to differences in antibiotic susceptibilities compared to other NTM species.


Optimization of physical dose distributions with hadron beams: comparing photon IMRT with IMPT.
Intensity modulated radiotherapy with high enery photons (IMRT) and with charged particles (IMPT) refer to the most advanced development in conformal radiation therapy. Their general aim is to increase local tumor control rates while keeping the radiation induced complications below desired thresholds. IMRT is currently widely introduced in clinical practice. However, the more complicated IMPT is still under development. Especially, spot- scanning techniques integrated in rotating gantries that can deliver proton or light ion-beams to a radiation target from any direction will be available in the near future. We describe the basic concepts of intensity modulated particle therapy (IMPT). Starting from the potential advantages of hadron therapy inverse treatment planning strategies are discussed for various dose delivery techniques of IMPT. Of special interest are the techniques of distal edge tracking (DET) and 3D-scanning. After the introduction of these concepts a study of comparative inverse treatment planning is presented. The study aims to identify the potential advantages of achievable physical dose distributions with proton and carbon beams, if different dose delivery techniques are employed. Moreover, a comparison to standard photon IMRT is performed. The results of the study are summarized as: i) IMRT with photon beams is a strong competitor to intensity modulated radiotherapy with charged particles. The most obvious benefit observed for charged particles is the reduction of medium and low doses in organs at risk. ii) The 3D-scanning technique could not improve the dosimetric results achieved with DET, although 10-15 times more beam spots were employed for 3D-scanning than for DET. However, concerns may arise about the application of DET, if positioning errors of the patient or organ movements have to be accounted for. iii) Replacing protons with carbon ions leads to further improvements of the physical dose distributions. However, the additional degree of improvement due to carbon ions is modest. The main clinical potential of heavy ion beams is probably related to their radiobiological properties.


3'nucleotidase/nuclease in protozoan parasites: Molecular and biochemical properties and physiological roles.
3'-nucleotidase/nuclease (3'NT/NU) is a bi-functional enzyme that is able to hydrolyze 3'-monophosphorylated nucleotides and nucleic acids. This review summarizes the major molecular and biochemical properties of this enzyme in different trypanosomatid species. Sequence analysis of the gene encoding 3'NT/NU in Leishmania and Crithidia species showed that the protein possesses five highly conserved regions that are characteristic of members of the class I nuclease family. 3'NT/NU presents a molecular weight of approximately 40 kDa, which is conserved among the studied species. Throughout the review, we discuss inhibitors and substrate specificity, relating them to the putative structure of the enzyme. Finally, we present the major biological roles performed by 3'NT/NU. The involvement of 3'NT/NU in the purine salvage pathway was confirmed by the increase of activity and expression of the enzyme when the parasites were submitted to purine starvation. The generation of extracellular adenosine is also important to the modulation of the host immune response. Interaction assays involving Leishmania parasites and macrophages indicated that 3'-nucleotidase activity increases the association index between them. Recently, it was shown that 3'NT/NU plays a role in parasite escape from neutrophil extracellular traps, one of the first mechanisms of the host immune system for preventing infection.


Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves two different cell surface molecules.
Streptococcus pyogenes, or group A Streptococcus, is one of the most frequent causes of pharyngitis and skin infections in humans. Many virulence mechanisms have been suggested to be involved in the infectious process. Among them is the binding to the bacterial cell surface of the complement regulatory proteins factor H, factor H-like protein 1 (FHL-1), and C4b-binding protein. Previous studies indicate that binding of these three regulators to the streptococcal cell involves the M protein encoded by the emm gene. M-type 18 strains are prevalent among clinical isolates and have been shown to interact with all three complement regulators simultaneously. Using isogenic strains lacking expression of the Emm18 or the Enn18 proteins, we demonstrate in this study that, in contradistinction to previously described S. pyogenes strains, M18 strains bind the complement regulators factor H, FHL-1, and C4b-binding protein through two distinct cell surface proteins. Factor H and FHL-1 bind to the Emm18 protein, while C4BP binds to the Enn18 protein. We propose that expression of two distinct surface structures that bind complement regulatory proteins represents a unique adaptation of M18 strains that enhances their resistance to opsonization by human plasma and increases survival of this particular S. pyogenes strain in the human host. These new findings illustrate that S. pyogenes has evolved diverse mechanisms for recruitment of complement regulatory proteins to the bacterial surface to evade immune clearance in the human host.


DNA polymorphism and linkage disequilibrium within the apolipoprotein CII locus on human chromosome 19.
The gene for human apolipoprotein CII (APOCII) is located on the proximal long arm of chromosome 19. It has been established as a closely linked marker for myotonic dystrophy (DM), the most common form of adult muscular dystrophy. In the present linkage study, we have analysed 6 APOCII RFLPs in 213 haplotypes: TaqI, 3.8/3.5 kb; BgII, 12.0/9.0 kb; BanI, 2.5/1.6 kb; BamHI, 6.0/4.9 kb; NcoI, 14.5/11.5 kb, and AvaII, 0.6/0.4 kb. The polymorphic enzyme sites were determined to be present at the following frequencies: TaqI, 0.43; BglI, 0.51; BanI, 0.25; BamHI, 0.99; NcoI, 0.51, and AvaII, 0.52. Ordering of the polymorphic sites, 5'----3', has been determined to be (NcoI-BglI)-AvaII-BanI-TaqI. Significant disequilibrium was seen between 5 of the APOCII RFLPs.


Arachidonate metabolites, platelet-activating factor, and the mobilization of protein kinase C in human polymorphonuclear neutrophils.
In contrast to our previous report (Biochem. Biophys. Res. Comm. 134:587, 1986), we now find that protein kinase C (PKC) is mobilized in human polymorphonuclear neutrophils (PMN) stimulated with platelet-activating factor (PAF) or leukotriene (LT)B4. Thus nanomolar concentrations of each compound caused PMN to lose cytosolic, PKC-specific protein phosphorylating activity, as well as receptors for phorbol myristate acetate (PMA). Smaller gains in membrane-associated PMA receptors accompanied these changes. Diacylglycerol and PMA had very similar effects on PKC. However, unlike these direct PKC activators, PAF and LTB4 induced only moderate decreases in cytosolic PKC; acted only on PMN pretreated with cytochalasin B; did not mobilize PKC in disrupted PMN or activate PKC in a cell-free system; and with respect to PAF, induced responses that partially reversed within 30 min. Furthermore, PAF, LTB4, and several of their structural analogues mobilized PKC at concentrations correlating closely with their respective affinities for cellular LTB4 or PAF receptors. Thus PAF and LTB4 acted by indirect and apparently receptor-mediated mechanisms. Four observations indicated that the cytochalasin B-dependent degranulating actions of PAF and LTB4 involved PKC. First, PKC mobilization and degranulation occurred at the same stimulus concentrations. Second, 5-hydroxyicosatetraenoate dramatically enhanced both PKC mobilization and degranulation when elicited by PAF; it had relatively little influence on LTB4-induced responses. Third, PAF-induced mobilization (t1/2 less than 7 sec) preceded degranulation (t1/2 approximately 20 sec). Finally, a PKC blocker, polymyxin B, was similarly effective in inhibiting degranulation responses to PAF, LTB4, and PMA. Because stimulated PMN may produce and use PAF, LTB4, and 5-hydroxyicosatetraenoate as secondary intracellular mediators, our results implicate PKC as a central and potentially critical regulator of function.


Role of endogenous TGF-beta in glucocorticoid-induced lung type II cell differentiation.
In the fetal lung, endogenous transforming growth factor (TGF)-beta inhibits early morphogenesis and blocks hormone-induced type II cell differentiation. We hypothesized that endogenous TGF-beta inhibits type II cell differentiation and that the stimulatory effects of glucocorticoids result in part from suppression of TGF-beta. Epithelial cells were isolated from human fetal lung and cultured under defined conditions with and without dexamethasone plus cAMP to promote type II cell differentiation. Control cells produced TGF-beta, which was activated in part by alpha(V)beta(6)-integrin. Treatment with dexamethasone, but not cAMP, reduced TGF-beta1 and -beta2 transcripts and TGF-beta bioactivity in culture medium. To examine the effects of decreased TGF-beta in the absence of glucocorticoid, cells were treated with antibodies to TGF-beta and its receptors. By real-time RT-PCR, antibody blockade of TGF-beta reduced serpine1, a TGF-beta-inducible gene, and increased gene expression for sftpa, sftpb, sftpc, and titf1, mimicking the response to hormone treatment. By microarray analysis, 29 additional genes were induced by both TGF-beta antibody and hormone treatment, and 20 other genes were repressed by both treatments. For some genes, the fold response was comparable for antibody and hormone treatment. We conclude that endogenous TGF-beta suppresses expression of surfactant proteins and selected other type II cell genes in fetal lung, in part secondary to increased expression of titf1, and we propose that the mechanism of glucocorticoid-induced type II cell differentiation includes antagonism of TGF-beta gene suppression. Surfactant production during fetal development is likely influenced by relative levels of TGF-beta and glucocorticoids.


Surface Stabilized InP/GaP/ZnS Quantum Dots with Mg Ions for WLED Application.
One of the most highlighted cadmium-free quantum dots (QDs), InP-based QDs, have improved their optical properties. However, InP-based QDs have some practical drawbacks, for example, stability, compared with CdSe-based QDs. Poor stability of InP-based QDs yields critical problems, such as agglomeration and photoluminescence quenching in light emitting diode (LED). It has to be solved for applications and most research has focused on thick outer shells as an effective solution. We introduced magnesium cations for improving stability of InP-based QDs. We applied very small amounts of Mg cations as surface stabilizers, as a result, stability of QDs is clearly improved. Then, QD based LED chips also yield improved values including RA of 84.4, CCT of 3799 K, and luminous efficiency of 129.57 Im/W, which are highly improved data compared with our previous results.


High precision (14 bit), high density (octal) analog to digital converter for spectroscopy applications.
Nuclear and particle physics experiments with large number of detectors require signal processing and data collection strategies that call for the ability to collect large amount of data while not sacrificing the precision and accuracy of the data being collected. This paper deals with the development of a high precision pulse peak detection, analog to digital converter (ADC) module with eight independent channels in plug-in daughter card motherboard model, best suited for spectroscopy experiments. This module provides multiple channels without cross-talk and of 14 bit resolution, while maintaining high density (each daughter card has an area of just 4.2(")x0.51(")) and exhibiting excellent integral nonlinearity (< or = +/-2 mV or +/-0.02% full scale reading) and differential nonlinearity (< or = +/-1%). It was designed, developed and tested, in house, and gives added advantages of cost effectiveness and ease of maintenance.


Social encouragement can influence manual preference in 6 month-old-infants.
The purpose of this study was to investigate the influence of social encouragement on infants' hand movements, in particular on manual preference. Thirty-six infants were observed at 5.5 months. In a first step, their spontaneous manual preference was recorded with an object placed at the midline position. The second step consisted in encouraging infants to use their non-preferred hand by putting the object near that hand and congratulating them. The third step was similar to the first one (object placed at the midline position) except that the infant continued to be congratulated when (s)he used the non-preferred hand for reaching the object. Results showed that half of the infants exhibited a spontaneous manual preference and that a majority of these infants could use their non-preferred hand when verbally encouraged. Moreover, infants showing a left hand preference modified their hand-use more easily than infants showing a right hand preference. Although our findings reveal only a temporary and short-term influence of the social context, results are discussed in light of a socio-cognitive perspective whereby social encouragement can model manual preference, in particular its strength and stability. Highlights • At 5.5 months, a manual preference was observed in 47.2% of the infants. • The preference for the left hand was observed in 35.3% of the infants who presented a manual preference. • Left-handers change more easily their hand-use than right handers.


Exploiting nucleotide thiophosphates to probe mechanistic aspects of Escherichia coli DNA gyrase.
The interaction of DNA gyrase with ATP has been probed using a range of thiophosphate ATP analogs. ATP gammaS is not detectably hydrolyzed by gyrase but can support limited, probably catalytic, DNA supercoiling. ATP gammaS is a good inhibitor of both ATP hydrolysis and ATP-supported supercoiling. In contrast, both ATP alphaS(Rp) and ATP betaS(Rp) have been shown to be good substrates for the ATPase reaction of gyrase and to support catalytic DNA supercoiling. The corresponding Sp diastereoisomers do not support significant levels of supercoiling and are not readily hydrolyzed, but are shown to be reasonable inhibitors of gyrase. For ATP alphaS(Rp), the supercoiling and ATPase activities appear to be tightly coupled with the thionucleotide being apparently a better substrate than ATP in terms of both DNA supercoiling and nucleotide hydrolysis. In the case of ATP betaS(Rp), DNA supercoiling and nucleotide hydrolysis appear to be uncoupled in that ATP betaS(Rp) is almost as good a substrate as ATP for the ATPase reaction of both intact gyrase and the 43 kDa GyrB fragment, whereas it only supports slow DNA supercoiling; the mechanistic consequences of these observations are discussed in terms of a new model for energy coupling in gyrase. DNA gyrase has been shown to be capable of catalyzing DNA supercoiling in the presence of Mg2+, Ca2+, and Mn2+ but not Zn2+, Co2+, Ni2+, or Cd2+. The pronounced diastereoselectivity seen in both the DNA supercoiling and ATPase activity with ATP alphaS and ATP betaS together with evidence from the X-ray structure of the 43 kDa GyrB-ADPNP-Mg complex is consistent with metal ion coordination at both of these sites, and probably to the gamma-phosphoryl center during turnover. Thus, the absolute configuration of the catalytically active Mg2+-ATP complex is likely to involve coordination to the pro-S oxygens at both P alpha and P beta, leading to the alpha,beta,gamma-tridentate Mg-ATP complex with the lambda-exo configuration.


Grafting and Depositing Lithium Polysulfides on Cathodes for Cycling Stability of Lithium-Sulfur Batteries.
Based on dissolution/deposition chemistry, together with multielectron redox reactions, lithium-sulfur (Li-S) batteries have been demonstrated as a promising energy storage system. However, the diffusion of soluble lithium polysulfide intermediates (LiPSs) to bulk electrolyte results in the fast capacity fade of a Li-S cell. How to confine the LiPSs within the cathode while retaining high reversible capacity remains a huge challenge. In this work, N-bromophthalimide, an organic molecule with an aromatic heterocyclic ring and a reactive halogen bond, is introduced as an electrolyte additive to conquer the excessive dissolution and diffusion of LiPSs by in situ formation of an organopolysulfide deposition layer. This electrochemically active layer not only maintains the internal sulfur conversion but also prevents LiPSs from diffusing into the electrolyte bulk, thereby improving the cycling and rate performance of Li-S batteries. This study provides a feasible strategy for regulating the reaction region and path for high-performance Li-S batteries.


Fabrication and Applications of Potentiometric Membrane Sensors Based on γ-Cyclodextrin and Calixarene as Ionophores for the Determination of a Histamine H1-Receptor Antagonist: Fexofenadine.
Supramolecular fexofenadine sensors have been constructed. Although noncovalent intermolecular and intramolecular interactions, which are far weaker than covalent contacts, are the main focus of supramolecular chemistry, they can be used to create sensors with an exceptional affinity for a target analyte. The objective of the current research study is to adapt two PVC membrane sensors into an electrochemical approach for the dosage form determination of histamine H1-receptor antagonists: fexofenadine. The general performance characteristics of two new modified potentiometric membrane sensors responsive to fexofenadine hydrochloride were established. The technique was based on the employment of γ-cyclodextrin (CD) (sensor 1), 4-tert-butylcalix[8]arene (calixarene) (sensor 2) as an ionophore, potassium tetrakis (4-chlorophenyl) borate (KTpClPB) as an ion additive, and (o-NPOE) as a plasticizer for sensors 1 and 2. The sensors showed fast responses over a wide fexofenadine concentration range (1 × 10-2 to 4.5 (4.7) × 10-6 M), with detection limits of 1.3 × 10-6 M and 1.4 × 10-6 M for sensors 1 and 2, respectively, in the pH range of 2-8. The tested sensors exhibit the fexofenadine near-Nernstian cationic response at 56 and 58 mV/decade for sensors 1 and 2, respectively. The sensors exhibit good stability, fast response times, accuracy, precision, and longer life for fexofenadine. Throughout the day and between days, the sensors exhibit good recovery and low relative standard deviations. Fexofenadine in its pure, dose form has been identified with success using the modified sensors. The sensors were employed as end-point indications for the titration of fexofenadine with NaTPB.


Transformation using in vivo and in vitro methylation in Streptomyces griseus.
Streptomyces griseus does not readily take up foreign DNA isolated from other Streptomyces species or Escherichia coli, presumably due to its unique restriction-modification systems that function as a barrier for interspecific DNA transfer. To efficiently transform S. griseus by avoiding the restriction barriers, we methylated incoming DNA in vivo and in vitro and treated protoplasts with heat prior to transformation. Whereas heat treatment of protoplasts or methylation of the E. coli-Streptomyces shuttle vectors (pXE4 and pKK1443) did not prominently improve the transformation efficiency, HpaII methylation of the vectors from any E. coli strains tested in this study highly increased the transformation efficiency. The highest transformation efficiency was observed when the shuttle vectors were isolated from the dam, hsd strain of E. coli (GM161) and methylated by AluI and HpaII methyltransferases, and the efficiency was approximately the same as that of the vectors from S. griseus. We identified several restriction-modification systems that decrease the transformation efficiency. This research also led us to understand methylation profiles and restriction-modification systems in S. griseus.


Retrospective analysis of epidemiological aspects of Vibrio vulnificus infections in Korea in 2001-2010.
In this study, we performed a retrospective, quantitative analysis of the epidemiological aspects and risk factors of Vibrio vulnificus infections in Korea from 2001 to 2010. In a total of 588 V. vulnificus infection cases (prevalence rate, 0.12 cases/100,000 persons), 285 were fatal (case-fatality rate [CFR], 48.5%). Males were more significantly infected by V. vulnificus than females (86.1% versus 13.9%; P < 0.01), and a higher incidence of V. vulnificus infections was observed in people aged more than 40 years (95.1%; P < 0.01). Moreover, most V. vulnificus infections occurred in the unemployed (42.0%; P < 0.01). The seasonal patterns of outbreaks revealed that most outbreaks occurred in June (early summer) throughout November (the end of autumn) (99.6%; P < 0.01), and significantly more outbreaks occurred in the southern part (65.3%) of the Korean peninsula compared with those in the northern (29.4%) and central (5.3%) parts (P < 0.01). In addition, the number of V. vulnificus infections was significantly higher in rural and coastal villages (69.9%) than in urban areas (30.1%) (P < 0.01). In conclusion, because of the rapid aggravation and high CFR of V. vulnificus infections, public health education should strongly recommend avoiding raw seafood products and limited exposure to marine water during the summer.


Theoretical and Experimental Studies on the Signal Propagation in Soil for Wireless Underground Sensor Networks.
Wireless Underground Sensor Networks (WUSNs), an important part of Internet of things (IoT), have many promising applications in various scenarios. Signal transmission in natural soil undergoes path loss due to absorption, radiation, reflection and scattering. The variability and dynamic of soil conditions and complexity of signal attenuation behavior make the accurate estimation of signal path loss challenging. Two existing propagation models for predicting path loss are reviewed and compared. Friis model does not consider the reflection loss and is only applicable in the far field region. The Fresnel model, only applicable in the near field region, has not considered the radiating loss and wavelength change loss. A new two stage model is proposed based on the field characteristics of antenna and considers four sources of path loss. The two stage model has a different coefficient m in the near field and far field regions. The far field distance of small size antenna is determined by three criteria: 2 D2/λ, 5 D, 1.6 λ in the proposed model. The proposed two stage model has a better agreement with the field experiment data compared to Friis and Fresnel models. The coefficient m is dependent on the soil types for the proposed model in near field region. It is observed from experiment data that the m value is in the range of 0~0.20 for sandy soils and 0.433~0.837 for clayey silt.


Genetic and biochemical evidence that EBNA 2 interaction with a 63-kDa cellular GTG-binding protein is essential for B lymphocyte growth transformation by EBV.
Epstein-Barr virus (EBV) nuclear protein 2 (EBNA 2) is an acidic transcriptional transactivator of virus and cell gene expression and is essential for growth transformation of primary B lymphocytes. EBNA 2 transactivation of response elements (E2REs) can be mediated by interaction with a GTGGGAA-specific DNA-binding factor(s). We now purify the factor by S-Sepharose and EBNA 2 affinity chromatography and identify it as a single 63-kDa protein. The protein is shown to specifically coimmunoprecipitate with EBNA 2 from lymphoblasts transfected with an EBNA 2 FLAG expression vector. Mutation of GTG to TCT in a GTGGGAA motif common to the Cp, LMP2, and LMP1 promoters results in loss of recognition by p63. EBNA 2 amino acids 310-336 are sufficient for p63 binding. The only motif in this 27 amino acid sequence which is common to the EBNA 2 genes of EBV types 1 and 2 is GPPWWPP (I/V) (C/R) DP, which is therefore likely to mediate p63 interaction. Mutation of WW to SS or FF ablates interaction with p63, indicating that both the hydrophobic and aromatic characteristics of WW are essential for its "key" interaction with p63. EBNA 2 with a WW mutated to SS is also unable to marker rescue primary B lymphocyte transforming virus from cells infected with an EBNA 2-deleted virus, while otherwise isogenic wild-type EBNA 2 readily marker rescues transforming virus in parallel experiments. EBNA 2 transactivation through the Cp E2RE is completely abolished by the WW to SS mutation while transactivation of -234 to +40 LMP1 E2RE is only partially affected. These genetic and biochemical experiments support the hypothesis that EBNA 2 WW interaction with a p63 GTGGGAA-binding protein is essential for EBV-mediated cell growth transformation because it specifically associates EBNA 2 with its response elements. This enables the EBNA 2 acidic domain to transcriptionally transactivate specific genes.


3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance. Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine. Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect. We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance.


Bringing nature to the fore.
This article has two aims: first, to give an historic overview of the nature-nurture debate in relation to how mothers learn to breastfeed. The overview will relate how the 'nurture' perspective came to dominate our understanding of the ontogeny of breastfeeding. The second aim is to propose professional breastfeeding competencies in an attempt to integrate the 'nature' perspective within early breastfeeding support. These are under development and written with a view to stimulating peer review and discussion.


Compact multi-enzyme pathways in P. pastoris.
We report for the first time the functional simultaneous expression of nine genes from a single 2A peptide based polycistronic expression construct. The feasibility and arising opportunities for the biosynthetic pathway balancing for chemical production were demonstrated by the co-expression of the violacein and carotenoid biosynthesis pathways.


Compartment Syndrome After Isolated Closed Transverse Fibular Shaft Fracture.
In the lower extremity, compartment syndrome has been associated with fractures of the tibial plateau, shaft, and plafond. The patient was an 89-year-old male driver involved in a T-bone type motor vehicle accident. He sustained a closed transverse fibular shaft fracture and initially had fullness in his anterior/lateral compartments but no pain with passive and active range of motion of his ankle. Because of previous cardiac stenting, he was on dual anticoagulation therapy. Serial examination demonstrated tense compartments with notable pain during ankle range of motion. He was taken emergently to the operating room for four-compartment fasciotomies. On postoperative day 2, he returned to the operating room for débridement and underwent primary closure. The remainder of his hospital course was normal. Two-month follow-up did not demonstrate any compartment syndrome sequelae. In conclusion, patients on dual anticoagulation therapy are at a higher risk of developing compartment syndrome secondary to high-energy trauma, despite simple fracture patterns.


Supine exercise during lower body negative pressure effectively simulates upright exercise in normal gravity.
Exercise within a lower body negative pressure (LBNP) chamber in supine posture was compared with similar exercise against Earth's gravity (without LBNP) in upright posture in nine healthy male volunteers. We measured footward force with a force plate, pressure in soleus and tibialis anterior muscles of the leg with transducer-tipped catheters, calf volume by strain gauge plethysmography, heart rate, and systolic and diastolic blood pressures during two conditions: 1) exercise in supine posture within an LBNP chamber during 100-mmHg LBNP (exercise-LBNP) and 2) exercise in upright posture against Earth's gravity without LBNP (exercise-1 G). Subjects exercised their ankle joints (dorsi- and plantarflexions) for 5 min during exercise-LBNP and for 5 min during exercise-1 G. Mean footward force produced during exercise-LBNP (743 +/- 37 N) was similar to that produced during exercise-1 G (701 +/- 24 N). Peak contraction pressure in the antigravity soleus muscle during exercise-LBNP (115 +/- 10 mmHg) was also similar to that during exercise-1 G (103 +/- 13 mmHg). Calf volume increased significantly by 3.3 +/- 0.5% during exercise-LBNP compared with baseline values. Calf volume did not increase significantly during exercise-1 G. Heart rate was significantly higher during exercise-LBNP (99 +/- 5 beats/min) than during exercise-1 G (81 +/- 3 beats/min). These results indicate that exercise in supine posture within an LBNP chamber can produce similar musculoskeletal stress in the legs and greater systemic cardiovascular stress than exercise in the upright posture against Earth's gravity.


The continuum of comparability extends to biosimilarity: how much is enough and what clinical data are necessary?
Experts debate the clinical evidence standards needed to approve major manufacturing changes for biologics, biosimilars, and interchangeable biosimilars. As sponsors consider their development plans, the resource investment required to develop an analytically highly similar candidate must be balanced by regulatory relief for the clinical studies required to achieve the necessary indications for the marketed product. This article discusses biosimilarity and comparability as related scientific and regulatory concepts and the usefulness of clinical data for both.


Unraveling regulation and new components of human P-bodies through a protein interaction framework and experimental validation.
The cellular factors involved in mRNA degradation and translation repression can aggregate into cytoplasmic domains known as GW bodies or mRNA processing bodies (P-bodies). However, current understanding of P-bodies, especially the regulatory aspect, remains relatively fragmentary. To provide a framework for studying the mechanisms and regulation of P-body formation, maintenance, and disassembly, we compiled a list of P-body proteins found in various species and further grouped both reported and predicted human P-body proteins according to their functions. By analyzing protein-protein interactions of human P-body components, we found that many P-body proteins form complex interaction networks with each other and with other cellular proteins that are not recognized as P-body components. The observation suggests that these other cellular proteins may play important roles in regulating P-body dynamics and functions. We further used siRNA-mediated gene knockdown and immunofluorescence microscopy to demonstrate the validity of our in silico analyses. Our combined approach identifies new P-body components and suggests that protein ubiquitination and protein phosphorylation involving 14-3-3 proteins may play critical roles for post-translational modifications of P-body components in regulating P-body dynamics. Our analyses provide not only a global view of human P-body components and their physical interactions but also a wealth of hypotheses to help guide future research on the regulation and function of human P-bodies.


Anthropometry in Klinefelter syndrome--multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism.
Klinefelter syndrome, 47, XXY (KS), is underdiagnosed partly due to few clinical signs complicating identification of affected individuals. Certain phenotypic traits are common in KS. However, not all aspects of the KS phenotype are well described. To describe anthropometry and body composition in KS and relate findings to biochemistry and X-chromosome related genetic markers. Seventy three KS males referred to our clinic and 73 age-matched controls underwent comprehensive measurements of anthropometry and body composition in a cross-sectional, case-controlled study. Furthermore, genetic analysis for parental origin of the supernumerary X-chromosome, skewed X-chromosome inactivation and androgen receptor (AR) CAG repeat length was done. Anthropometry and body composition in KS and the effect of genotype hereon. KS males were taller (absolute difference: 5.1 cm, P < .001) with longer legs (5.7 cm, P < .001) compared with controls. Furthermore, 2D:4D was increased in KS males (relative effect size: Cohen's d = 0.40), reflecting reduced fetal testosterone exposure. Also, bi-iliac width (0.41), waist (0.52), and hip circumference (0.47) (P < .02 for all), as well as total fat mass (0.74), abdominal fat mass (0.67), and total body fat percentage (0.84) was increased in KS males (P < .001 for all), while bitesticular volume was reduced (4.6). AR CAG repeat length was comparable in KS and controls, and among KS CAG correlated to arm length (P = .04), arm span (P = .01), and leg length (P = .04). Effects of parental origin of the supernumerary X-chromosome and skewed X-chromosome inactivation were negligible. Anthropometry and body composition in KS is specific and dysmorphic and affected by AR CAG repeat length and decreased exposure to testosterone already during fetal life.


Site-directed mutagenesis of Pro327 in the lac permease of Escherichia coli.
By use of oligonucleotide-directed, site-specific mutagenesis, Pro327 in the lac permease of Escherichia coli has been replaced with Ala, Gly, or Leu. Permease with Ala at position 327 catalyzes lactose/H+ symport in a manner indistinguishable from wild-type permease. Permease with Gly at position 327, on the other hand, exhibits about one-tenth the activity of wild-type permease but catalyzes lactose accumulation to essentially the same steady-state level as wild-type permease. Finally, permease with Leu at position 327 is completely inactive. The results demonstrate that there is no relationship between permease activity and the helix-breaking (Pro and Gly) or helix-making (Ala and Leu) properties of the residue at position 327. It is suggested that it is primarily a chemical property of the side chain at position 327 (i.e., bulk, hydropathy, and/or ability to hydrogen bond) that is critical for activity and that neither cis/trans isomerization of Pro327 nor the presence of a kink at this position is important.


Smad3 and Bmal1 regulate p21 and S100A4 expression in myocardial stromal fibroblasts via TNF-α.
Bmal1, a clock gene, is associated with depression, hypertrophy, metabolic syndrome and diabetes. Smad3, which is involved in the TGF-β signaling pathway, plays an important role in the regulation of tumor progression, fibrosis, obesity and diabetes. Our previous report showed that Smad3 has circadian expression in mouse livers. In the current study, we focused on the heart, especially on the myocardial stromal fibroblasts because the roles of Bmal1 and Smad3 in this tissue are poorly understood. Bmal1 and Smad3 have circadian expression in mouse hearts, and their circadian expression patterns were similar. Bmal1 expression decreased in the hearts of whole-body Smad3 knockout mice, whereas Smad3 expression had little effect on heart-specific Bmal1 knockout mice. Both Smad3 knockout and heart-specific Bmal1 knockout mice showed increases in p21, S100A4, CD206 and TNF-α expression in the myocardial stromal fibroblasts and macrophage compared to control mice. We also examined Smad3, Bmal1 and Dec1 expression in human tissue from old myocardial infarctions. Expression of Smad3, Bmal1 and Dec1 decreased in the stromal fibroblasts of tissue from old myocardial infarctions compared to control cases. On the other hand, p21, S100A4 and TNF-α increased in the stromal fibroblasts of tissue from old myocardial infarctions. Furthermore, expression of Smad3, Bmal1 and Dec1 decreased in TNF-α treated-NIH3T3 cells but expression of p21 and S100A4 increased. This new evidence suggests that Smad3 and Bmal1 regulate p21 and S100A4 expression in myocardial stromal fibroblasts through TNF-α.


Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer.
Pancreatic inflammation appears to increase the risk of pancreatic cancer. This observation is striking in the hereditary pancreatitis kindreds but also occurs in alcoholic, idiopathic, and tropical chronic pancreatitis and cystic fibrosis. However, the mutations associated with hereditary pancreatitis or cystic fibrosis are not found in sporadic pancreatic adenocarcinomas, suggesting that the effects are indirect by causing recurrent pancreatitis and chronic inflammation. The process of mutation accumulation and clonal expansion that is required for development of invasive pancreatic adenocarcinoma must therefore be accelerated in chronic pancreatitis to account for the high incidence of pancreatic cancer in these patients.


Screening and Management of Gestational Diabetes Mellitus after Bariatric Surgery.
Gestational diabetes mellitus (GDM) is a frequent medical complication during pregnancy. This is partly due to the increasing prevalence of obesity in women of childbearing age. Since bariatric surgery is currently the most successful way to achieve maintained weight loss, increasing numbers of obese women of childbearing age receive bariatric surgery. Bariatric surgery performed before pregnancy significantly reduces the risk to develop GDM but the risk is generally still higher compared to normal weight pregnant women. Women after bariatric surgery therefore still require screening for GDM. However, screening for GDM is challenging in pregnant women after bariatric surgery. The standard screening tests such as an oral glucose tolerance test are often not well tolerated and wide variations in glucose excursions make the diagnosis difficult. Capillary blood glucose measurements may currently be the most acceptable alternative for screening in pregnancy after bariatric surgery. In addition, pregnant women after bariatric surgery have an increased risk for small neonates and need careful nutritional and foetal monitoring. In this review, we address the risk to develop GDM after bariatric surgery, the challenges to screen for GDM and the management of women with GDM after bariatric surgery.


A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery.
To assess clinical efficacy of IV paracetamol 1 g and IV metamizol 1 IV metamizol 1 g on a 24-h dosing schedule in this randomized, double-blinded, placebo-controlled study of 38 ASA physical status I-III patients undergoing retinal surgery. General anaesthesia using remifentanil, propofol, and desflurane was performed for surgery. The patients were randomly allocated to three groups, receiving infusions of paracetamol 1 g/100 mL (Para Group), of metamizol 1 g/100 mL (Meta Group), or of 100 mL of saline solution as placebo control (Plac Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to intravenous opioid rescue medication. The primary efficacy variables were pain scores at rest over 30 h postoperatively analysed by using repeated ANOVA measurement. Secondary efficacy variables were pain scores on coughing, also analysed by repeated ANOVA measurement. Five patients in the Plac Group and one patient in the Meta Group interrupted the study protocol. Regarding pain scores at rest, Mauchly-test of sphericity was significant (p = 0.03). For the p time effects a significant result was detected (p < 0.001). The main effect between the three treatment groups was significantly different (p = 0.01). The Bonferroni adjusted pair wise comparisons between p the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.024; mean difference 14.8; p 95% CI 1.6-28.0), between the Plac Group and the Meta Group in favour of IV metamizol (p = 0.025; mean difference 14.4; 95% CI p 1.5-27.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; mean difference 0.4; 95% CI-12.8 to 13.6). Pain scores on coughing showed a significant different main effect between the three treatment groups (p = 0.022). The Bonferroni adjusted pair wise comparisons between the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.032; mean difference 17.9; 95% CI 1.3-34.6), a p difference, though not reaching statistical significance, in favour of IV metamizol between the Plac Group and the Meta Group (p = 0.081; p mean difference 15.0; 95% CI -1.4 to 31.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; p mean difference 2.9; 95% CI -13.8 6 to 19.6). None of the patients experienced itching; one patient in the Meta Group developed a mild erythema. There was no statistical difference in the incidence of nausea (Plac vs. Para Group: p = 0.94, Plac vs. Meta Group: p = 0.98, Para vs Meta Group: p = 0.95) or vomiting (Plac vs. Para Group: p = 0.73, Plac vs. Meta Group: p = 0.85, Para vs Meta Group: p = 0.86) between the groups. Patients in the Plac Group experienced significantly more often sedation than patients in the Meta Group (p = 0.049). There was a trend of higher sedation in the Plac Group than in the Para Group, which did not reach statistical significance (p = 0.07). There was no difference in sedation between the Meta and the Para Groups (p = 0.84). IV paracetamol 1 g has a similar analgesic potency as IV metamizol 1 g for postoperative analgesia after retinal surgery.


The healing forearm fracture: a matched comparison of forearm refractures.
Forearm fractures in children usually heal rapidly after closed treatment. Recent studies report forearm refracture rates of 5%. The purpose of this study was to identify risk factors for refracture based on radiographic variables. We performed a retrospective review of patients that sustained a second forearm fracture (refracture) between 1998 and 2005. Refractures were defined as having a second fracture of the same forearm within 18 months of the original fracture. A comparison group of single-fracture patients followed in a capitated insurance plan were included and matched based on age and sex. Radiographic assessment included initial/final angulation, displacement, and fracture-line visibility at latest follow-up. Sixty-three refractures were compared with 132 age- and sex-matched single-fracture patients. Time to refracture averaged 10 months. Thirty-eight percent of the initial fractures in the refracture group occurred in the proximal or middle third of the forearm compared with 15% for the single-fracture patients (P < 0.001). Because location of the fracture was found to be a risk factor for refracture, a secondary analysis was performed with refracture patients matched to single-fracture patients based on age, sex, bone fractured, fracture location, and treatment method. Fracture-line visibility of the radius at latest follow-up was clearly visible in 48% of refractures compared with 21% of controls (P = 0.05). Initial fracture severity and residual deformity were not significantly different. Proximal and middle one third forearm fractures are at greater risk of refracture compared with distal one third forearm fractures. There was a trend toward incomplete healing seen more commonly in those that refractured, emphasizing the importance of longer immobilization in these fractures. Prognostic study, level III, case-control study.


Content characteristics driving the diffusion of antismoking messages: implications for cancer prevention in the emerging public communication environment.
This study examined how content characteristics of antitobacco messages affect smokers' selective exposure to and social sharing of those messages. Results from an experiment revealed that content features predicting smokers' selection of antismoking messages are different from those predicting whether those messages are shared. Antismoking messages smokers tend to select are characterized by strong arguments (odds ratio = 2.02, P = .02) and positive sentiments (odds ratio = 3.08, P = .03). Once selected, the messages more likely to be retransmitted by smokers were those with novel arguments (B = .83, P = .002) and positive sentiments (B = 1.65, P = .005). This research adds to the literature about the content characteristics driving the social diffusion of antitobacco messages and contributes to our understanding of the role of persuasive messages about smoking cessation in the emerging public communication environment.


A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid tissue.
cDNA encoding a novel putative G-protein-coupled receptor, named LyGPR (lymphocyte derived G-protein-coupled receptor) was cloned using a reverse transcription-PCR approach. The LyGPR amino acid sequence is 375 residues long and shows similarity (about 30-35% identity) both to the angiotensin receptors and members of the chemokine receptor family. Northern blot analysis revealed a 3.1-kb LyGPR transcript expressed predominantly in lung, heart and lymphoid tissues. LyGPR expression was also detected in the pre-B acute lymphoblastoid leukemia cell lines Reh and Nalm-6, in the Burkitt's lymphoma line Daudi, and in hematopoietic progenitor cells from bone marrow, as well as in B cells, T cells and monocytes from peripheral blood.


Novel corrugated In9 anionic layer in Li2Y5In9: square pyramidal In5 clusters interconnected by unusual butterfly In4 clusters.
The new ternary polar intermetallic phase, Li2Y5In9, was obtained by high-temperature solid-state reactions of the corresponding elements inwelded Ta tubes. Its crystal structure was established by a single-crystal X-ray diffraction study. Li2Y5In9 crystallizes in the tetragonal space group P4/nmm (No. 129) with cell parameters of a = b = 10.1242(4), c = 15.1091(10) A and Z = 4. The structure of Li2Y5In9 features a two-dimensional corrugated anionic In9 layer composed of two types of square pyramidal In5 units and butterfly In4 units. There are two types of square pyramidal In5 units: one with normal In-In bonds and another one with greatly elongated In-In separations within its In4 square. Packing of these 2D In9 layers resulted in cavities and tunnels that are occupied by Y and Li atoms. Extended-Hückel tight-binding calculations indicate that Li2Y5In9 is metallic.


Medium optimization for hen egg white lysozyme production by recombinant Aspergillus niger using statistical methods.
Statistics-based experimental design was used to investigate the effect of medium components (starch, peptone, ammonium sulfate, yeast extract, and CaCl2.2H2O) on hen's egg white lysozyme production by Aspergillus niger HEWL WT-13-16. A 2(5-1) fractional factorial design augmented with center points revealed that peptone, starch, and ammonium sulfate were the most significant factors, whereas the other factors were not important within the levels tested. The method of steepest ascent was used to approach the proximity of optimum. This task was followed by a central composite design to develop a response surface for medium optimization. The optimum medium composition for lysozyme production was found to be: starch 34 g L-1, peptone 34 g L-1, ammonium sulfate 11.9 g L-1, yeast extract 0.5 g L-1, and CaCl2.2H2O 0.5 g L-1. This medium was projected to produce, theoretically, 212 mg L-1 lysozyme. Using this medium, an experimental maximum lysozyme concentration of 209+/-18 mg L-1 verified the applied methodology.


Proenkephalin predicts acute kidney injury in cardiac surgery patients.
Acute kidney injury (AKI) occurs in up to 40% of patients undergoing cardiac surgery. Proenkephalin A 119-159 (pro-ENK) is a novel, stable surrogate biomarker for enkephalins, endogenous opioids involved in various physiological processes, including neurohormonal stress. 92 patients undergoing cardiac surgery at the Veterans Affairs San Diego Healthcare System had a post-hoc analysis performed to determine the ability of pro-ENK to predict AKI as well as to compare it against other risk factors for development of AKI. Of 92 patients, 20 patients developed AKI post-operatively. Pro-ENK levels were significantly elevated in patients who develop AKI. Log pro-ENK value pre-operatively has an odds ratio of 23.8 (p = 0.011, 95% CI = 2 - 270) in its association with AKI. Pro-ENK performs similarly to baseline creatinine in its ability to predict post-operative AKI. Importantly, pro-ENK has a strong positive correlation with creatinine (r = 0.806). Additionally, changes in pro-ENK level, from pre-operatively to 12 hours post-operatively have greatest area under curve by ROC analysis for AKI after post-operative day 1. Pro-ENK is associated with prediction of AKI in patients undergoing cardiac surgery. Pro-ENK likely has decreased clearance in the setting of AKI. However, future studies analyzing this novel biomarker should be considered to further elucidate its clinical utility and to better understand mechanisms of renal injury.


Effect of low-level light therapy on diabetic foot ulcers: a near-infrared spectroscopy study.
Diabetic foot ulcer (DFU) is a diabetic complication due to peripheral vasculopathy and neuropathy. A promising technology for wound healing in DFU is low-level light therapy (LLLT). Despite several studies showing positive effects of LLLT on DFU, LLLT's physiological effects have not yet been studied. The objective of this study was to investigate vascular and nervous systems modification in DFU after LLLT. Two samples of 45 DFU patients and 11 healthy controls (HCs) were recruited. The total hemoglobin (totHb) concentration change was monitored before and after LLLT by near-infrared spectroscopy and analyzed in time and frequency domains. The spectral power of the totHb changes in the very-low frequency (VLF, 20 to 60 mHz) and low frequency (LF, 60 to 140 mHz) bandwidths was calculated. Data analysis revealed a mean increase of totHb concentration after LLLT in DFU patients, but not in HC. VLF/LF ratio decreased significantly after the LLLT period in DFU patients (indicating an increased activity of the autonomic nervous system), but not in HC. Eventually, different treatment intensities in LLLT therapy showed a different response in DFU. Overall, our results demonstrate that LLLT improves blood flow and autonomic nervous system regulation in DFU and the importance of light intensity in therapeutic protocols.


Thiazolidinedione use and post-operative atrial fibrillation: a US nested case-control study.
Previous investigations suggested thiazolidinediones (TZDs) have the ability to suppress inflammation. Since the pathophysiology of atrial fibrillation (AF) after cardiothoracic surgery (CTS) likely involves an inflammatory mechanism, we sought to determine whether preoperative use of TZDs could further reduce the incidence of post-CTS AF in a population treated with beta-blockers and prophylactic amiodarone. All diabetic patients over the age of 50 years, not in atrial arrhythmia prior to surgery, who underwent CTS from the Atrial Fibrillation Suppression Trials I, II and III (AFIST I, II and III) were evaluated in this nested case-control study. Patient demographics, surgical characteristics, medication utilization and the incidence of post-CTS AF (AF > 5 minutes duration) were collected as part of AFIST I, II and III. Multivariate logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals (CIs). One hundred and eighty-four diabetic patients were enrolled in the three trials. Overall, the study population averaged 66.9 +/- 7.3 years of age, 71.7% were male, 7.1% underwent valve surgery, 4.9% had prior AF, 17.9% had heart failure and 84.2% and 41.8% received postoperative beta-blockade and prophylactic amiodarone, respectively. Forty patients (21.7%) received a preoperative TZD and 144 (78.3%) did not. In total, 66 patients (35.9%) developed post-CTS AF. Upon multivariate logistic regression, the preoperative use of TZDs was found to be associated with a 20% non-statistically significant reduction in post-CTS AF (adjusted odds ratio; 0.80, 95% CI 0.32-1.99; p = 0.63). Patients were not randomized to receive TZDs or not. We may not have had adequate power to evaluate our post-CTS AF endpoint. In a diabetic population treated perioperatively with beta-blocker and amiodarone, adjunctive TZD use was associated with a non-statistically significant reduction in a patient's odds of developing post-CTS AF. Further research is needed to determine whether TZDs, in fact, do not have anti-fibrillatory effects or whether our study was underpowered to detect a statistically significant benefit with TZDs.


Association between Serum Albumin, Insulin Resistance, and Incident Diabetes in Nondiabetic Subjects.
Serum albumin has been suggested to be associated with insulin resistance. We evaluated the association between serum albumin concentration and insulin resistance. We also investigated whether serum albumin level has an independent effect on the development of diabetes. In our study, 9,029 subjects without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into tertiles based on their serum albumin levels at baseline. The odds ratio (OR) for the prevalence of insulin resistance, defined as the top quartile of homeostasis model assessment of insulin resistance and the presence of impaired fasting glucose and nonalcoholic fatty liver disease, was evaluated cross-sectionally. Also, the hazard ratio (HR) for incident diabetes was estimated longitudinally, according to the baseline albumin tertiles using Cox proportional hazard analysis respectively. From the lowest to the highest tertile of albumin, the multivariable-adjusted ORs of insulin resistance increased significantly in both men and women. During the mean follow-up period of nearly 4 years, 556 (6.1%) subjects progressed to diabetes. The multivariable-adjusted HR (95% confidence interval [CI]) of diabetes in men were 1, 1.09 (95% CI, 0.86 to 1.40), and 1.10 (95% CI, 0.86 to 1.41), respectively, from the lowest to the highest tertiles of baseline albumin. Corresponding values for women were 1, 1.21 (95% CI, 0.66 to 2.21), and 1.06 (95% CI, 0.56 to 2.02), respectively. Our study showed that increased serum albumin level was associated with insulin resistance. However, serum albumin did not have an independent effect on the development of diabetes.


Wound management of ulcerated haemangioma of infancy - an audit.
Haemangioma of infancy, a benign tumour of blood vessels, is the most common tumour of infancy. Ulceration, the most common complication, presents a unique wound care challenge. A retrospective audit of medical records of children with haemangioma of infancy who presented to the Royal Children's Hospital, Melbourne, Australia, between January 2000 and December 2014 was undertaken with an aim to examine wound management of ulcerated haemangioma of infancy. In total, 535 hospital medical records were identified as suitable, of which 352 were randomly selected and audited, of which 84 patients had ulcerated haemangioma of infancy, and 62 were subject to wound management. Of these, 35 were successfully managed by wound dressings, 9 were not fully healed at the time of last review, and 18 were referred for surgical excision. Patients attended an average of five outpatient visits, and the average time from presentation to documented healing was 105 days. There were a total of 225 episodes of wound dressing, for which there was a documented follow-up appointment at which healing could be assessed. Although a wide range of dressings were used, there was no clear pattern of benefit of one dressing over another. Wounds were less likely to be healed after the use of a silver-impregnated dressing. Pain was poorly documented. Clinical assessment of whether wounds were infected was of no help in planning treatment. There is considerable variability in the management of this difficult wound group, and further prospective studies are required.


Lymph nodes of onchocerciasis patients after treatment with ivermectin: reaction of eosinophil granulocytes and their cationic granule proteins.
Lymph node and skin biopsies from Liberian patients with generalized and localized (sowda) onchocerciasis were studied 12-68 hours after oral administration of ivermectin at a single dose of 150 micrograms/kg body weight. Electron microscopic examination and immunohistochemical staining with antibodies against two different forms of eosinophil cationic protein (ECP EG1, ECP EG2), eosinophil peroxidase (EPO) and cationic leukocyte antigen (CLA) were performed. Following their disappearance from the skin, a large number of microfilariae was found in the regional lymph nodes. The lymph nodes from treated patients had over ten times more eosinophils compared to those from untreated persons with a peak of eosinophil density at 40-48 hours after treatment. Degenerating microfilariae in the lymph nodes were encircled by eosinophils, which showed positive immunostaining for ECP, EPO or CLA. Intra- and extracellular eosinophil granules revealed a great variation in their condition. In some specific granules a variety of structural alterations in the crystalloid cores occurred while in others different stages of deficiency in the matrix electron density were observed. The frequent necrosis of eosinophils in the immediate vicinity and at some distance from the microfilariae, with subsequent release of granules and the deposition of toxic cationic granule proteins onto the microfilarial cuticle during the eosinophil-parasite adherence reaction, demonstrated the function of these proteins in the ivermectin-reinforced killing of microfilariae in lymph nodes.


Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons.
Neurons are highly polarized cells. They give rise to several dendrites but only one axon. In addition, many neurons show a preferred orientation. For example, pyramidal neurons of the cerebral cortex extend their apical dendrites toward the cortical surface while their axons run in opposite direction toward the white matter. This characteristic orientation reflects the migratory trajectory of a pyramidal cell during cortical development: the leading process (the future apical dendrite) extends toward the marginal zone (MZ) and the trailing process (the future axon) toward the intermediate zone (IZ) while the cells migrate radially to reach their destination in the cortical plate (CP). In this review article, we summarize the function of Reelin, an extracellular matrix protein synthesized by Cajal-Retzius cells in the MZ, in the development of the characteristic orientation of the leading processes running perpendicular to the cortical surface. Reelin promotes migration toward the cortical surface since late-generated cortical neurons in the reeler mutant are unable to reach upper cortical layers. Likewise, Reelin is important for the orientation and maintenance of the leading processes of migrating neurons since they are misoriented in the developing reeler cortex, as are the apical dendrites of pyramidal cells in the mature mutant. Reelin-induced phosphorylation of cofilin, an actin-associated protein, is crucial since pyramidal neurons transfected by in utero electroporation (IUE) with a non-phosphorylatable form of cofilin (cofilinS3A) show severe migration defects reminiscent of those in the reeler mutant. Remarkably, migration of neurons in the cortex of reeler mice was partially rescued by transfecting them with LIM kinase 1 (LIMK1), the kinase that induces phosphorylation of cofilin at serine3, or with a pseudo-phosphorylated cofilin mutant (cofilinS3E). Together these results indicate that Reelin-induced phosphorylation of cofilin is an important component in the orientation and directed migration of cortical neurons and in their correct lamination.


Ventilatory control in patients with sleep apnoea and left ventricular dysfunction: comparison of obstructive and central sleep apnoea.
Sleep apnoea is common in patients with heart failure. While most patients have central sleep apnoea (CSA), a minority have obstructive sleep apnoea (OSA). The pathophysiology of CSA is not well understood. We hypothesized that central chemosensitivity would be an important pathophysiological factor in patients with CSA, and not in OSA. The aim of this study was to compare ventilatory responses between patients with CSA and those with OSA. Acute ventilatory responses to eucapnic hypoxia and hyperoxic hypercapnia were measured during wakefulness in 34 patients (33 males and one female, aged 59+/-8 yrs (mean+/-SD)), with stable medically-treated left ventricular dysfunction (LVD) and sleep apnoea (18 OSA and 16 CSA). Patients with CSA had a decreased awake end-tidal carbon dioxide tension (4.1+/-0.5 kPa), increased ventilatory response to carbon dioxide (0.65+/-0.43 L.min.(-1).kPa PCO2(-1)), and eucapnic hypoxic responses in the normal range (0.6+/-0.4 L.min(-1)/% fall in arterial oxygen saturation (Sa,O2)). In contrast, patients with OSA had normal end-tidal carbon dioxide tension (4.9+/-0.5 kPa), and normal ventilatory responses to hypercapnia (0.29+/-0.16 L.min(-1).kPa PCO2(-1)) and hypoxia (0.5+/-0.5 L-min(-1)/% fall in Sa,O2). These findings suggest that augmented chemosensitivity to hypercapnia may be an important factor in the pathophysiology of central sleep apnoea in patients with heart failure.


[Biochemical typing of Enterobacter isolated from several clinical materials].
A total of 74 Enterobacter species have been isolated from the patients applying to the department of Microbiology, University of Ankara, Studying several biochemical test systems their strains have been found. 37 of these Enterobacter species have been found to be Enterobacter cloacae, 10 Enterobacter agglomerans, 13 Enterobacter aerogenes, 3 Enterobacter hafniae (Hafnia alvei), 1 Enterobacter sakazakii. 2 of the strains couldn't be classified. In conclusion most of the strains were found to be Enterobacter cloacae.


Amphiphilic four-helix bundle peptides designed for light-induced electron transfer across a soft interface.
A family of four-helix bundle peptides were designed to be amphiphilic, possessing distinct hydrophilic and hydrophobic domains along the length of the bundle's exterior. This facilitates their vectorial insertion across a soft interface between polar and nonpolar media. Their design also now provides for selective incorporation of electron donor and acceptor cofactors within each domain. This allows translation of the designed intramolecular electron transfer along the bundle axis into a macroscopic charge separation across the interface.


State dependent ring polymer molecular dynamics for investigating excited nonadiabatic dynamics.
A recently proposed nonadiabatic ring polymer molecular dynamics (NRPMD) approach has shown to provide accurate quantum dynamics by incorporating explicit state descriptions and nuclear quantizations. Here, we present a rigorous derivation of the NRPMD Hamiltonian and investigate its performance on simulating excited state nonadiabatic dynamics. Our derivation is based on the Meyer-Miller-Stock-Thoss mapping representation for electronic states and the ring-polymer path-integral description for nuclei, resulting in the same Hamiltonian proposed in the original NRPMD approach. In addition, we investigate the accuracy of using NRPMD to simulate the photoinduced nonadiabatic dynamics in simple model systems. These model calculations suggest that NRPMD can alleviate the zero-point energy leakage problem that is commonly encountered in the classical Wigner dynamics and provide accurate excited state nonadiabatic dynamics. This work provides a solid theoretical foundation of the promising NRPMD Hamiltonian and demonstrates the possibility of using the state-dependent RPMD approach to accurately simulate electronic nonadiabatic dynamics while explicitly quantizing nuclei.